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M6112 > L6: Embryo Implantation and Development > Flashcards

L6: Embryo Implantation and Development Flashcards

1
Q

What is the infertility rate for couples in the UK?

A
  • 1 in 6
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2
Q

Where and when does fertilisation occur?

A
  • Ampulla region of fallopian tube
  • Day 0
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3
Q

Outline the stages of early embryo development: (including timing)

A
  • Fertilisation -> zygote
  • First cleavage around day 1 -> 2 cell stage
  • 4-cell
  • 8-cell uncompacted morula
  • 8-cell compacted morula (day 4)
  • Early blastocyst (blastulation; day 5)
  • Late stage blastocyst, hatched
  • Implantation (day 8-9)
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4
Q

Regions of fallopian tube (ovary -> uterus)

A
  • Fimbriae (attached to ovary)
  • Infundibulum
  • Ampulla
  • Isthmus
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5
Q

Blastulation and gastrulation outline:

A
  • Blastulation: Formation of blastocoel (fluid filled sac) alongside inner cell mass
  • Gastrulation: Differentiation of inner cell mass into 3 distinct layers
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6
Q

When does the uterus become receptive?

A
  • Mid-secretory phase
  • Day 19-23
  • Commonly known as window of implantation
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7
Q

4 stages of implantation

A
  • Orientation
  • Apposition
  • Attachment
  • Invasion
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8
Q

Give the 3 essential factors for embryo implantation:

A
  • Healthy embryo at blastocyst stage
  • Implantation window (receptive endometrium)
  • Effective communication between the two
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9
Q

Outline the role of the zona pellucida during oogenesis and fertilisation:

A
  • Supports communication between oocytes and follicle
  • Offers protection during development (mechanical stress and polyspermy)
  • Regulates interactions between ovulated eggs and free-swimming sperm during and following fertilization
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10
Q

Components of the blastocyst with role:

A
  • Blastocoel cavity (fluid-filled, supports gastrulation)
  • Inner cell mass (source of embryonic stem cells; will provide cell lineages for body)
  • ZP: degenerates and decomposes during hatching to be replaced by trophoblast cells
  • Trophoblasts (provide nutrients to embryo and later develop into large part of placenta)
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11
Q

3 phenotypical features of the pre/non-receptive endometrium:

A
  • Long apical microvilli
  • High surface negative charge
  • Thick mucin layer
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12
Q

Features of receptive endometrium:

A
  • Shortening of microvilli
  • Loss of surface negative charge
  • Thinning of mucin coat
  • Formation of pinopodes
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13
Q

Features and function of the glycocalyx in EECs:

A
  • Covers surface of EECs
  • Antiadhesive properties, able to form gel-like layer of heavily glycosylated mucin (MUC1)
  • Protects endometrial surface from infection
  • Provides lubrication
  • May act to deter blastocyst implantation
  • Selectively cleared by presence of competent blastocyst
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14
Q

Role of pinopodes in EECs:

A
  • Cytoplasmic projections arising from apical surface of EEC
  • Revealed upon glycocalyx clearing -> allow attachment to take place
  • Help blastocyst to be exposed to EEC
  • Progesterone dependent (inhibited by presence of oestrogen)
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15
Q

What is decidualisation? How is it intitiated?

A
  • Significant changes to cells of endometrium (preparing for and during pregnancy)
  • Differentiation of elongated, fibroblast-like mesenchymal cells in uterine stroma into rounded, epithelioid-like cells
  • Signalled via Cox-2, allowing PG synthesis (calcium involvement) -> e.g. blastocyst secretes trypsin which stimulates calcium signalling via various pathways
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16
Q

Functions of decidualised stromal cells:

A
  • Secretory phenotype (IGFBP-1 and PRL particularly important secreted factors)
  • Can regulate trophoblast invasion
  • Able to dampen maternal immune response (e.g. uNK cells), providing resistance to immune and oxidative insult
  • Decidualisation is crucial in vascularisation and angiogenesis (VEGFs and angiopoietin have a role in this)
  • Decidual breakdown products are an important source of histiotrophic nutrition in very early stages after implantation
17
Q

Molecular messages of attachment:

A
  • Removal of mucin-1 (locally to blastocyst in humans)
  • Upregulation of LIF in the gland cells by progesterone -> shift from proliferative state of epithelium to differentiated state (breakdown of cell-cell junctions)
  • -> LIF Also affects stroma (driving proliferation via EGF-signalling)
  • Adhesion molecules: integrins, selectins, e-cadherins (EMT) expressed on blastocyst interacting with counterparts in ECM of decidua
  • Expression of HB-EGF -> allows zonal hatching, promotes blastocyst growth
  • Secrete IL-1 (affects invasion effects)
18
Q

Molecular messages of invasion: (Core)

A
  • MMPs -> break down matrix in stroma
  • TIMPs -> keep MMPs in check
  • Both stimulating and regulatory factors in balance; invasion, is inherently an inflammatory process so must be very carefully controlled
  • They are regulated by IL-1 which begins to be secreted by blastocyst during attachment
19
Q

List 2 endometrial factors for implantation failure

A
  • Thin endometrium
  • Altered expression of adhesive molecules/immunological factors
20
Q

List 4 embryonic factors for implantation failure:

A
  • Genetic abnormalities
  • Sperm defects
  • Embryonic aneuploidy
  • Zona hardening (inappropriate)
21
Q

What are the three stages of embryonic development:

A
  • Germinal (2 weeks) aka embryogenic phase
  • Embryonic (6 weeks)
  • Fetal (10+ weeks)
22
Q

When and where is hCG first beginning to be released?

A
  • as early as 6-7 days post-fertilisation
  • Synthesised by trophoblast of invading blastocyst
23
Q

For each germ layer, give examples of key cell fates:

A
  • Endoderm (inner): Lung, thyroid, digestive cells
  • Mesoderm (middle): Muscle (cardiac/skeletal/smooth), RBCs, kidney tubule cells
  • Ectoderm (external): Skin, neurons, pigment cells
  • Note that these 3 layers form upon gastrulation
24
Q

Why is maintenance of the corpus luteum critical during the first 12 weeks of pregnancy? Give two signals for its maintenance:

A
  • Corpus luteum produces progesterone
  • Progesterone is essential for proliferation and differentiation of stromal cells of endometrium (decidualisation)
  • Prolonged progesterone production is stimulated by hCG from trophoblast cells
  • Placenta takes over function of corpus luteum at around 12 week point
  • Secretion of luteal relaxin is also important in preventing luteolysis (i.e. preventing CL breakdown)
25
Q

Define viviparous:

A
  • Species that produce live young
26
Q

Define monotocous:

A
  • Species that have (ideally) single offspring per pregnancy
27
Q

What changes does compaction enact on the morula?

A
  • Maximising cell-cell contacts
  • Phenotypical change: radially symmetrical -> highly polarised epithelioid
28
Q

Give the 2 key roles of ZP in blastulation:

A
  • Prevents blastomeres of conceptus from falling apart (would result in monozygotic twins)
  • Prevents 2 genetically distinct conceptuses from sticking together to form a chimaeric complex
29
Q

What occurs during the embryonic phase?

A
  • Various embryonic cell and tissue types differentiate
  • Basic body plan laid down
30
Q

Humans show invasive implantation. What species show non-invasive implantation and what are the key differences seen?

A
  • Non-invasive implantation: Pigs, sheep, cow, horse
  • Epithelium remains largely intact and may be incorporated into the stroma
  • Attachment occurs later after the embryo is more developed
  • The extraembryonic tissue is particularly well developed, allowing larger surface area for nutrient uptake
  • Diffuse placenta will typically form
  • Don’t typically see decidual reaction in underlying stroma
  • Circulatory systems remain fairly distinct
31
Q

Features of the trophoectoderm at implantation stage:

A
  • Synctiotrophoblasts: terminally differentiated outer layer, secretory phenotype
  • Cytotrophoblasts: inner layer, stem cell population
32
Q

Discuss the vascular changes taking place during blastocyst invasion in humans; how do early embryos get their nutrition?

A
  • Trophoblast cells destroy walls of maternal spiral arterioles
  • This is important in remodelling them to support the implanted embryo
  • Need to become low-pressure sinusoidal sacs where the embryo can bathe in maternal blood
  • Note that embryos get their nutrition through histiotrophic means for the first 12 weeks (i.e. decidual breakdown products and glandular secretions), with haemotrophic support kicking in much later than implantation stage
33
Q

What signalling is crucial for establishment of the placenta?

A
  • Placental villi are formed following remodelling of ECM through tissue degradation
  • The implanted blastocyst must secrete serine proteases, MMPs, collagenases in order to infiltrate the basement membrane of the tissue
  • One key serine protease in plasminogen activator (plasminogen catalyses proteolysis of ECM)
34
Q

What mechanisms negatively regulate trophoblastic invasion?

A
  • Plasminogen activator inactivator 1
  • TIMPs
  • Both of these are upregulated by TGF-B secreted by Decidua
  • TGFB also provides antiproliferative signals to the trophoectoderm, promoting differentiation into synctiotrophoblasts
  • Embryo itself also expresses TGF-B -> binds to decorin (decidual PG) -> negative regulation of proliferation and migration

M6112 (15 decks)

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